The objective of this research project is a detailed elucidation of the effects of acute and chronic ethanol intoxication, and the effects of ethanol and acetaldehyde in vitro, on the subcellular fractions of skeletal and cardiac muscle. We have demonstrated that, in vitro, ethanol interferes with the binding and release of Ca2 ion by isolated membranes of the sarcoplasmic reticulum. Using highly purified cardiac plasma membranes we have shown that both ethanol and acetaldehyde inhibit the Na ion-K ion-activated ATPase activity of these membranes. Thus ethanol and acetaldehyde interfere with the supply of energy and intracellular ionic transport. Ca2 ion transport has been shown to be modified by cyclic AMP-dependent protein kinase, the effect of which is to stimulate Ca 2 ion transport. This is associated with phosphorylation of a protein in the membrane of the sarcoplasmic reticulum. The inhibitory effect of ethanol on oxalate-facilitated cardiac microsomal Ca2ion transport are more prominent in the case of microsomes in which calcium transport has been stimulated by cAMP-PK. Thus ethanol may "sensitize" the sarcoplasmic reticulum so that phosphorylation is reduced. On the other hand, the "activated" state of Ca2 ion transport may be more sensitive to ethanol. Using muscle protein isolated from the human and baboon tissues, we have found that after chronic ethanol ingestion, the contractility of the isolated protein, as measured by superprecipitation, is reduced. In vitro, ethanol and acetaldehyde inhibit the dissociation and reassociation of actin and myosin. Experiments are under way to clarify the mechanisms behind these effects.